Preliminary investigations demonstrated that grafts of murine mammary tumor cell suspensions are able to reinstate hemopoiesis in lethally irradiated recipients. Since this ability has been attributed exclusively to hemopoietic stem cells originating in blood forming tissues, our first priority is to establish the origin of the radioprotective cells in tumor tissue. We expect to accomplish this by assaying the hemopoietic capacity and tumorigenicity of mammary tumor-derived cells which can be identified by chromosome markers and antigenic specificity. The extent of the donor contribution to the stem cell component of the tumor will be determined by serial passage of mammary tumor cells in stem cell-deficient recipients and by appropriate in vitro cell segregation methods. The in vitro tumor cell lines also will be used to assess the effects of growth regulating factors on tumorigenicity and hemopoietic potential in vivo. Since it has been demonstrated that the hemopoietic system is significantly affected by mammary tumor growth and is involved in the transport of the infective tumor virus, it is important to determine the nature of this involvement. This will be investigated by monitoring the changes in stem cell populations of hemopoietic and tumor tissues during growth of the primary tumor and during its evolution from an adenocarcinoma to an anaplastic carcinoma. This information should be useful in understanding some of the mechanisms underlying neoplastic transformation of mammary epithelium and the nature of the host-tumor relationship.